The China Post news staff
June 4, 2014, 12:00 am TWN
TAIPEI, Taiwan -- A National Cheng Kung University (NCKU) team has discovered the pathogenesis of liver fibrosis and developed antibodies that reduce liver damage, inhibit hepatic fibrosis and recover liver function, according to a press release from the school. Ming-shi Chang, chair professor of biochemistry and molecular biology at NCKU, led the team to make another breakthrough in their research on interleukin 20 (IL-20), said the NCKU.
Currently, NCKU has been granted a patent in the United States, which has attracted great interest from the biotechnology industry, the university said.
Hepatitis, fatty liver disease, and hepatotoxicity are some of the primary disorders that lead to the development of liver diseases, according to Chang, who added that inflammation of the liver can evolve into liver fibrosis and cirrhosis, and patients in the final stages of liver cirrhosis often develop liver cancer.
Inflammation is the source of many diseases, said Chang. She also said that IL-20 is involved in several inflammatory diseases.
Chang's team discovered that IL-20 is a primary cause of liver diseases, and they confirmed that the liver tissue of patients with liver fibrosis, liver cirrhosis and liver cancer have significantly higher levels of IL-20. IL-20 causes liver inflammation and increases the development of the extracellular matrix, thus causing liver fibrosis and cirrhosis, the NCKU stated.
IL-20 is a protein secreted by the human immune system, Chang said. An excessive amount of IL-20 can damage body tissue and, therefore, lead to many diseases such as osteoporosis and a variety of liver diseases, said the NCKU.
Most liver diseases result from liver damage caused by long-term chronic hepatitis. Patients with liver disease include people infected with the hepatitis B and C viruses, as well as alcoholic hepatitis and toxin-induced hepatitis.
Repeated or prolonged chronic hepatitis can seriously damage liver cells. This damage stimulates fibroblasts in the liver to produce collagen fibers, which are then deposited in the liver and fill up the empty spaces left by dead hepatocytes. Finally, this fibrosis causes liver cirrhosis, the NCKU stated.
Chang and her research team observed that patients with liver fibrosis, liver cirrhosis and liver cancer also had high levels of IL-20. After investigating this phenomenon, they discovered that IL-20 activates hepatic stellate cells and stimulates transforming growth factor (TGF)-beta1, tumor necrosis factor (TNF)-alpha as well as Type I Collagen in these cells to increase the accumulation of the extracellular matrix.
Because IL-20 is a protein secreted by the human body, Chang and her research team developed an anti-IL-20 monoclonal antibody, which inhibits the functions of IL-20 and stops IL-20-induced liver damage at the same time.
Chang's research has provided a solution to the therapeutic management of liver fibrosis and a new direction for treating liver diseases, said the NCKU.
Their research titled “IL-20 and IL-20R1 antibodies protect against liver fibrosis” has been published in the May issue of Hepatology.
Source
Also See:
Hepatology. 2014 Apr 25. doi: 10.1002/hep.27189. [Epub ahead of print]
IL-20 and IL-20R1 antibodies protect against liver fibrosis.
- 1Institute of Biopharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.
Interleukin (IL)-20 is a proinflammatory cytokine of the IL-10 family and involved in rheumatoid arthritis, atherosclerosis, stroke, and osteoporosis. However, the pathophysiological roles of IL-20 in liver injury have not been extensively studied. We explored the involvement of IL-20 in liver injury and the therapeutic potential of IL-20 antagonists for treating liver fibrosis. Compared with the normal liver tissue from healthy individuals, the amount of IL-20 was much higher in hepatocytes and hepatic stellate cells in liver biopsies from patients with fibrosis, cirrhosis, and hepatocellular carcinoma. Carbon tetrachloride (CCl4 ) treatment induced IL-20 that further upregulated the expression of transforming growth factor (TGF)-β1 and p21WAF1 and resulted in cell cycle arrest in the Clone-9 rat hepatocyte cell line. IL-20 activated quiescent rat hepatic stellate cells (HSCs) and upregulated TGF- β1 expression. IL-20 also increased TGF- β1, tumor necrosis factor (TNF)-α, and type I collagen (Col-I) expression, and promoted the proliferation and migration of activated HSCs. Serum IL-20 was significantly elevated in mice with short-term and long-term CCl4 -induced liver injury. In mice with short-term liver injury, anti-IL-20 monoclonal antibody (7E) and anti-IL-20 receptor (IL-20R1) monoclonal antibody (51D) attenuated hepatocyte damage caused by CCl4 , TGF- β1, and chemokine production. In mice with long-term liver injury, 7E and 51D inhibited CCl4 -induced cell damage, TGF- β1 production, liver fibrosis, HSC activation, and extracellular matrix (ECM) accumulation, which was caused by the reduced expression of tissue inhibitors of metalloproteinases (TIMPs) as well as increased metalloproteinase (MMP) expression and Col-I production. IL-20R1-deficient mice were protected from short-term and long-term liver injury. Conclusion: We identified a pivotal role of IL-20 in liver injury and showed that 7E and 51D may be therapeutics for liver fibrosis. (Hepatology 2014;).
Copyright © 2014 American Association for the Study of Liver Diseases.
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Copyright © 2014 American Association for the Study of Liver Diseases.
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